Determination of hydraulic head loss is one of the most important components of designing drip irrigation systems. For having an optimized water distribution in drippers, it is necessary that head loss in each section should be in predetermined range. In recent years, fluent software has been used greatly in hydraulic science and fluid mechanics for evaluation of different flow regimes. The mentioned software has fantastic capabilities and its advantages have been proved in solving different fluid problems, mass and heat transfer. In the current study we tried to simulate hydraulic behavior of water flow in drip irrigation manifolds. Thus, three manifolds with same 18 meter length and outer diameter of 32, 40 and 50 millimeters which have 8 outlets with 2 meter intervals have been set. Validation of mentioned model has been done by comparing its result with observed values, measured in laboratory and computed results by Darcy Weisbach formula. In these experiments, pressure distribution was measured in three manifolds with different diameters and inlet pressure of 0.8, 1.0 and 1.2 bar using digital piezometer. Results showed that fluent software and Darcy Weisbach formula by having maximum relative error of 1.1268 and 0.5720 and correlation coefficient of 0.99959 and 0.99993, respectively in comparison of measured head loss are suitable models for simulation of water flow in manifolds and also are the appropriate and accurate methods in hydraulic simulation of water flow in drip irrigation systems